Do the current house dust mite-driven models really mimic allergic asthma?

Animal models play a key role in helping us determine the pathogenesis of diseases, and are vital for the discovery of new therapies and the improvement of existing medication. To do this, the model(s) need to closely mimic the clinical features and, where possible, be relevant to the disease in humans. Classically, the innocuous antigen ovalbumin (OVA) has been used to induce an allergic reaction in animals, and whilst it is possible to reproduce many of the features of the asthmatic lung, i.e. specific immunoglobulin (Ig)E levels, T-helper cell (Th)2-associated eosinophilic inflammation, early and late asthmatic responses (EAR and LAR, respectively), and airway hyperresponsiveness and associated tissue remodelling, researchers began to question the clinical relevance of using OVA as a model allergen [1]. In addition, it was commonly felt that the need for systemic delivery of OVA, with an adjuvant such as aluminium hydroxide, did not correctly mimic how asthmatic patients become sensitised to aeroallergens. To circumvent these issues, researchers switched to using topically delivered house dust mite allergen (HDM) to model allergic asthma [1], a route that, incidentally, is reported to induce tolerance when using OVA [2, 3]. A large proportion of human asthmatic patients have elevated levels of HDM-specific IgE and, after challenge with HDM, exhibit EAR, LAR and increases in airway inflammation [4–7]. For these reasons, the choice of HDM as the allergen to use in animal models seems like a logical one and explains the almost unilateral decision to switch to using them. Generally, these models are based around administering HDM topically into the airways, normally via the intranasal route, daily, over multiple weeks. This results in airway inflammation which features an increase in eosinophilia. However, a source of concern is the lack of evidence to show that the inflammation is part of an allergic (i.e. presence of HDM-specific IgE, B-cells and T-cells) phenotype. Unlike the classical OVA model, where, without prior sensitisation, airway inflammation is absent upon challenge, it is not clear whether HDM-induced inflammation is a truly allergic response or merely a consequence of repeated nasal insult with an inflammatory concoction. Indeed, it is possible to induce airway eosinophilia using a variety of non-IgE-associated stimuli, i.e. with Sephadex and endotoxin [8, 9]. The current dogma suggests that the line between ''sensitisa-tion'' and ''challenge'' phases is blurred in the repeated HDM insult models. But yet, if these models do have a strong allergic component one …